Identification of a novel boronic acid as a potent, selective, and orally active hormone sensitive lipase inhibitor. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Ogiyama, Tomoko; Yamaguchi, Mitsuhiro; Kurikawa, Nobuya; Honzumi, Shoko; Yamamoto, Yuka; Sugiyama, Daisuke; Inoue, Shinichi
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 16(2016)
• Page Start: 3801
• Page End: 3807
• Publication Date: 2016-08-15
• Subjects: Hormone sensitive lipase (HSL) -- Dyslipidemia -- Lipolysis -- Boronic acid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.06.022
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Hormone sensitive lipase (HSL) is an attractive therapeutic target of dyslipidemia. We designed and synthesized several compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound12 showing a potent HSL inhibitory activity with an IC50 value of 7 nM and a high selectivity against cholinesterases. Furthermore, compound12 is the first boron containing HSL inhibitor that has shown an antilipolytic effect in rats after oral administration at 3 mg/kg.